4-(1-menthoxymethyl)-2-phenyl-1,3-dioxolane or its derivatives and flavor composition containing the same

ABSTRACT

4-(1-menthoxymethyl)-2-phenyl-1,3-dioxolane or a derivative thereof represented by formula (I): ##STR1## wherein R 1  represents a hydrogen atom, a hydroxy group or a lower alkoxy group; R 2  and R 3 , which may be the same or different, each represents a hydrogen atom, a hydroxy group, a lower alkoxy group, or, when taken together, R 2  and R 3  represent a methylene dioxy group; useful in flavor compositions.

FIELD OF THE INVENTION

This invention relates to 4-(1-menthoxymethyl)-2-phenyl-1,3-dioxolane or its derivatives which are useful as an active ingredient for flavor or fragrance compositions.

BACKGROUND OF THE INVENTION

Various types of products incorporate ingredients which impart some kind of sensation to the mouth, oral cavity, throat or skin as a flavor or fragrance. Such products include toothpastes, mouthwashes, chewing gums, tobacco products, beverages and pharmaceutical products.

For example, 1-menthol and 3-(1-menthoxy)propane-1,2-diol are used as active ingredients in the products described above (e.g., as disclosed in U.S. Pat. No. 4,459,425). These products impart a cooling sensation to the mouth or skin.

PCT published application WO 92/10107 discloses that compound (II) represented by the following general formula: ##STR2## wherein R⁴ and R⁵ are independently --COOR⁶ wherein R⁶ is H or lower alkyl, provided that in at least one of R⁴ and R⁵, R⁶ is lower alkyl; wherein Z is a direct bond, or --CH═C(R⁷)--; where R⁷ is H or an alkyl group; and Y is a group of the formula (III) or (IV): ##STR3## where R⁸ and R⁹ are independently H, lower alkyl or --OR¹⁰ where R¹⁰ is H or lower alkyl; is useful as a flavor.

However, an ingredient which can impart a more significant and/or stimulating sensation is desired for the consumer market. Moreover, such an ingredient must have good quality and have a long-lasting taste, odor or combination thereof.

On the other hand, it has been disclosed that a substituted benzaldehyde acetal compound represented by general formula (V): ##STR4## wherein R¹¹ is C₁₋₂ alkyl, R¹² and R¹³ are each lower alkyl or R¹² and R¹³, together with oxygen atom to which they bond may form, a cyclic group of the formula --O--R¹⁴ --O-- where R¹⁴ is a lower alkylene or alkylalkylene which may be substituted with a lower alkyl or OH;

is useful as a flavor and a fragrance (as disclosed in JP-A-57-188537 and WO 94/06441) (The term "JP-A" as used herein means an "unexamined published Japanese patent application").

However, those compounds do not impart a stimulating sensation or a long-lasting sensation to the mouth or skin.

SUMMARY OF THE INVENTION

Accordingly, an object of this invention is to provide a new flavor and fragrance compound while meeting the above-described requirements.

In view of the above, extensive investigations have been conducted and, as a result, this invention provides 4-(1-menthoxymethyl)-2-phenyl-1,3-dioxolane or its derivatives with enhanced taste and odor and thus a long-lasting taste and odor is achieved.

The present invention provides 4-(1-menthoxymethyl)-2-phenyl-1,3-dioxolane or a derivative thereof represented by formula (I): ##STR5## wherein R¹ represents a hydrogen atom, a hydroxy group or a lower alkoxy group, R² and R³, which may be the same or different, each represents a hydrogen atom, a hydroxy group, a lower alkoxy group, or when taken together, R² and R³ represent a methylene dioxy group.

The present invention further provides a flavor or fragrance composition containing the compound of formula (I) or a derivative thereof as an active ingredient.

DETAILED DESCRIPTION OF THE INVENTION

In formula (I), the lower alkoxy group as represented by R¹, R² and R³ preferably contains from 1 to 4 carbon atoms, and specific examples thereof include a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, an n-butyloxy group and an isobutyloxy group.

More preferably, specific examples include a methoxy group and an ethoxy group.

Furthermore, specific examples of the preferred compound of the present invention represented by the formula (I), are compounds shown in Table 1 below, but the compounds of the formula (I) are not limited to these exemplified compounds.

In addition, in Table 1, Me, Et, Pr, and n-Bu represents a methyl group, an ethyl group, a propyl group, and an n-butyl group respectively.

                  TABLE 1                                                          ______________________________________                                         Compound                                                                               R.sup.1                                                                               R.sup.2   R.sup.3                                                                              Name                                            ______________________________________                                         1       H      H         H     4-(1-menthoxy-methyl)-                                                         2-phenyl-1,3-dioxolane-                                                        (Genzaldehyde-MPD)                              2       H      OH        OH    4-(1-menthoxy-methyl)-                                                         2-(3',4'-dihydroxy-                                                            phenyl)-1,3-dioxolane                                                          (protocatechuic alde-                                                          hyde-MPD)                                       3       H      OME       OH    4-(1-menthoxy-methyl)-                                                         2-(3'-methoxy-4'-hy-                                                           droxyphenyl)-1,3-di-                                                           oxolane (vanillin-MPD)                          4       H      OEt       OH    4-(1-menthoxy-methyl)-                                                         2-(3'-ethoxy-4'-hydroxy-                                                       phenyl)-1,3-dioxolane-                                                         (ethyl vanillin-MPD)                            5       OH     OMe       H     4-(1-menthoxy-methyl)-                                                         2-(2'-hydroxy-3'-                                                              methoxy-phenyl)-1,3-                                                           dioxolane(ortho vanillin-                                                      MPD)                                            6       H      H         OMe   4-(1-menthoxy-methyl)-                                                         2-(4'-methoxyphenyl)-                                                          1,3-dioxolane (anisal-                                                         dehyde-MPD)                                     7       H      --O--CH.sub.2                                                                            --O-- 4-(1-menthoxy-methyl)-                                                         2-(3',4'-methylenedioxy-                                                       phenyl)-1,3-dioxolane-                                                         (piperonal-MPD)                                 ______________________________________                                    

The abbreviations in Table 1 above are described below:

MPD represents an acetal of 3-(1-menthoxy)propanediol.

Of these compounds, preferred examples include Compound 2 and Compound 3.

4-(1-Menthoxymethyl)-2-phenyl-1,3-dioxolane or its derivatives of formula (I) can be produced, for example, using the following Reaction Scheme. ##STR6##

That is, 4-(1-menthoxymethyl)-2-phenyl-1,3-dioxolane or its derivatives of formula (I) can be easily synthesized by reaction of 3-(1-menthoxypropane-1,2-diol (2) with a benzaldehyde derivative (3) in the presence of an acid as a catalyst.

Examples of suitable benzaldehyde derivatives (3) include vanillin, protocatechuic aldehyde, ethyl-vanillin, ortho-vanillin, benzaldehyde, anisaldehyde and piperonal (heliotropin).

Suitable acids useful as a catalyst include any acid which is typically used in acetalization. Examples of suitable acids include hydrochloric acid, phosphoric acid, sulfuric acid, p-toluene sulfonic acid, acetic acid, anhydrous acetic acid, and propionic acid.

The reaction can be conducted in a similar manner to conventional acetalization chemistry.

It was found that the 4-(1-menthoxymethyl)-2-phenyl-1,3-dioxolane or its derivatives (I) obtained enhance taste or odor with a long-lasting taste and odor being produced.

Furthermore, it surprisingly turned out that the taste given off by the thus obtained 4-(1-menthoxymethyl)-2-phenyl-1,3-dioxolane or its derivatives (I) provides new and unexpected flavor characteristics.

For example, 4-(1-menthoxymethyl)-2-phenyl-1,3-dioxolane (Compound 3, vanillin-MPD) of the present invention has a hot, burning and tingling taste with a long-lasting taste.

Compound 3 is derived from vanillin and 3-(1-menthoxy)-1,2-propanediol. Vanillin is a common flavor or fragrance ingredient which is very sweet and has a strong vanilla-like odor. 3-(1-Menthoxy)-1,2propanediol (produced by TAKASAGO INTERNATIONAL CORPORATION, U.S. Pat. No. 4,459,425) is also a flavor or fragrance ingredient which has a menthol-like taste and a cooling effect.

That is, the character of Compound 3 of the present invention is different from that of those prior art compounds described above.

Compound (I) of the present invention can be used to prolong other sensations such as cooling sensations, for example, in combination with 1-menthol, 3-(1-menthoxy)-1,2-propanediol or isopulegol. When cooling and longer lasting tingling sensations are added together, the result would signal prolonged cooling effects to the user.

The burning tingling or bitter sensations are desirable as signals to convey to the user a desired psychological or physiological effect.

Compound (I) of the present invention can be used in confectionery, beverages and other foods. More specifically, it can be used in chewing gums, candies, ice creams, ice candies, chocolates, snacks, cookies, cakes, breads, tea, coffee, juice, fruit wine, dairy drinks, carbonated drinks, etc.

Also, Compound (I) of the present invention can be used in cosmetic and pharmaceutical products. More specifically, it can be used in mouthwashes, toothpastes, antiperspirant products, deodorant products, colognes, perfumes, lip sticks, soaps, shampoos, hair rinses and detergents, etc.

A suitable amount of 4-(1-menthoxymethyl)-2-phenyl-1,3-dioxolane or its derivatives (I) according to the present invention which is used in a flavor composition or in a fragrance composition to be used in various products is from 0.0001 to 10% by weight and preferably from 0.001 to 0.01% by weight based on the total weight of the composition.

The present invention is now illustrated in greater detail with reference to the following synthesis examples, examples and comparative examples. However, these synthesis examples, examples and comparative examples are not to be construed to limit the scope of the invention.

The analytical instruments used in the synthesis examples of the present specification were as follows:

(1) Nuclear magnetic resonance spectrum (¹ H-NMR):GSX-500 (500 MHz) (manufactured by JEOL)

(2) Mass spectrum (MS):JMS-DX303HF (manufactured by JEOL).

Unless otherwise indicated herein, all parts, percentages, ratios and the like are by weight.

SYNTHESIS EXAMPLE 1 Synthesis of Vanillin-MPD

To a 1.0 liter 2-neck round bottom flask, under a dry nitrogen atmosphere, was added 3,-1-menthoxypropane-1,2-diol (MPD)(17.0 g, 73.9 mmoles), followed by sequential addition of dry toluene (500 ml), vanillin (11.25 g, 73.9 mmoles) and p-toluene sulfonic acid monohydrate (141 mg, 0.74 mmoles).

The flask was equipped with a Dean-Stark apparatus filled with 3A molecular sieves. The mixture was refluxed under a dry nitrogen atmosphere for 42 hours at which time the reaction was determined to be complete by chromatographic analysis.

After cooling to room temperature (about 20° C.-30° C.), the solvent was removed under reduced pressure to obtain a crude oily residue. Purification of the crude oily residue by flash chromatography (silica gel Si-60, ethyl acetate/hexane=1/5 (by volume)) gave pure vanillin-MPD (17.8 g, 48.9 mmoles, 59.4% of theoretical yield).

¹ H-NMR (500 Mhz, CDCl₃, δ ppm): 0.76-0.09 (m, 11 H), 1.25 (m, 1H), 1.35 (m, 1H), 1.62 (m, hZ), 2.1 (m, 1H), 2.2 (m, 1H, 3.1 (m, 1H), 3.3 (m, 1/2H), 3.4 (m, 1/2H), 3.54 (m, 1H), 3.66 (m, 1/2H), 3.75 (m, 1/2H), 3.85 (m, 1/2H), 3.91 (s, 3H), 3.96 (m, 1/2H), 4.08 (m, 1/2H), 4.25 (m, 1/2H), 4.35 (m, 1H), 5.66 (s, 1H), 5.73 (s, 1/2H), 5.8 (s, 1/2H), 6.91 (m, 1H), 6.99 (m, 2H) MS (m/z): 364 (M+).

SYNTHESIS EXAMPLES 2 to 7

4-(1-Menthoxymethyl)-2-phenyl-1,3-dioxolane or its derivatives as shown in Table 2 below were prepared in the same manner as in Synthesis Example 1 above, except for replacing the substrate, vanillin, with each of the benzaldehyde or its derivatives as shown in Table 2 below.

                  TABLE 2                                                          ______________________________________                                         Synthesis          4-(1-Menthoxymethyl-2-                                                                          Isolated                                   Example            phenyl-1,3-dioxolane or its                                                                     Yield                                      No.    Substrate   Derivative Produced                                                                             (%)                                        ______________________________________                                         2      Protocatechuic                                                                             Protocatechuic   22.0                                              aldehyde    aldehyde-MPD                                                3      Ethyl vanillin                                                                             Ethyl vanillin-MPD                                                                              22.0                                       4      Ortho vanillin                                                                             Ortho vanillin-MPD                                                                              44.0                                       5      Benzaldehyde                                                                               Benzaldehyde-MPD 63.2                                       6      Anisaldehyde                                                                               Anisaldehyde-MPD 33.5                                       7      Piperonal   Piperonal-MPD    52.2                                       ______________________________________                                    

Spectral data for each is shown below.

Protocatechuic aldehyde-MPD

¹ H-NMR (500 Mhz, CDCl₃, δ ppm) : 5.64 (s, 1/2H, acetal), 5.80 (s, 1/2H, acetal), 6.55 (br s, 2H, --OH) MS (m/z): 350 (M⁺)

Ethyl vanillin--MPD

¹ H-NMR (500 Mhz, CDCl₃, δ ppm): 1.44 (t, 3H, --CH₃), 4.14 (q, 2H, --OCH₂ --), 5.72 (s, 1/2H, acetal), 5.72 (s, 1H, --OH), 5.83 (s, 1/2H, acetal) MS (m/z): 378 (M⁺)

Ortho-vanillin-MPD

¹ H-NMR (500 Mhz, CDCl₃, δ ppm): 3.82 (s, 3H, --OCH₃), MS (m/z): 364 (M⁺)

Benzaldehyde-MPD

¹ H-NMR (500 Mhz, CDCl₃, δ ppm): 5.80 (s, 1/2H, acetal), 5.93 (s, 1/2H, acetal) MS (m/z): 318 (M⁺)

Anisaldehyde-MPD

¹ H-NMR (500 Mhz, CDCl₃, δ ppm): 3.82 (s, 3H, --OHC₃), 5.76 (s, 1/2H, acetal), 5.88 (s, 1/2H, acetal) MS (m/z): 348 (M⁺)

Piperonal-MPD

¹ H-NMR (500 Mhz, CDCl₃, δ ppm): 5.71 (s, 1/2H, acetal), 5.96 (s, 1/2H, acetal), 5.96 (s, 2H, acetal) MS (m/z): 362 (M⁺)

EXAMPLE 1 Mouth Sensation of Compounds

Odor evaluation and mouth sensation evaluation were carried out on each compound synthesized in the foregoing Synthesis Examples. The results obtained are shown in Table 3 below.

                  TABLE 3                                                          ______________________________________                                                                            Longevity                                             Characteristic           of Mouth                                    Compound  Odor       Mouth Sensation                                                                              Sensation                                   ______________________________________                                         Vanillin-MPD                                                                             slight vanilla                                                                            hot, tingling, burn-                                                                         3-4 hours                                                        ing, numbing                                              Protocatechuic                                                                           --         hot, pepper, burning                                                                         3-4 hours                                   aldehyde-MPD                                                                   Ethyl     --         oily, metallic                                                                               --                                          vanillin-MPD                                                                   Ortho     --         bitter, slightly hot                                                                         --                                          vanillin-MPD                                                                   Benzaldehyde-                                                                            --         bitter        --                                          MPD                                                                            Anisaldehyde-                                                                            anisyl odor                                                                               slight sweet, 10-15                                       MPD                  slippery, creamy                                                                             minutes                                     Piperonal-MPD                                                                            slight floral                                                                             bitter        10 minutes                                            odor                                                                 ______________________________________                                    

EXAMPLE 2 Mouth Sensation Enhancement

Compounds of the present invention were tasted pure in small amounts on a wooden toothpick. Thermally hot tea was ingested after a short time.

The temperature of tea was determined subjectively by sipping a cup of tea. In the test, a small amount of vanillin-MPD was applied to the mouth via a wooden toothpick before sipping the tea. In the control, no addition treatment was used.

The compound of the present invention enhanced the thermally hot sensation to cause the tea to taste hotter in comparison with the tea consumed without the compound of this invention.

The results obtained are shown in Table 4 below.

                  TABLE 4                                                          ______________________________________                                                      Heat Determination                                                             Within 3 min.                                                                           After 30 min.                                            ______________________________________                                         Control        hot        warm                                                 Test Compound  very hot   hot                                                  ______________________________________                                    

EXAMPLE 3

A 1000 ppm ethanol solution of vanillin-MPD was prepared. Using this stock solution, a series of 5 ml samples of vanillin-MPD diluted with water were prepared at 100 ppm, 10 ppm and 1 ppm concentrations.

The procedure used for tasting the samples was as follows. The most dilute sample was tasted first. The sample was gargled for 30 seconds followed by spitting out the solution. Comments were recorded and the next sample was tasted when no effect of the previous sample remained in the mouth.

The results obtained are shown in Table 5 below.

                  TABLE 5                                                          ______________________________________                                                 Time                                                                   Vanillin-MPD                                                                             2-3 min.  10-15 min.                                                                               30 min.                                                                               120 min.                                  ______________________________________                                          1 ppm    bitter on                                                                      sides of                                                                       tongue,                                                                        slight                                                                         tingling,                                                                      numbing on                                                                     lips                                                                  10 ppm   very                                                                           bitter, hot                                                                    sensation                                                                      on roof of                                                                     mouth and                                                                      throat                                                               100 ppm   very hot  low level low level                                                                             low level                                           taste,    hot, sinus                                                                               hot, sinus                                                                            hot, sinus                                          bitter    clearing  clearing                                                                              clearing                                            taste     effect,   effect,                                                                               effect,                                                       numbing   numbing                                                                               numbing                                   ______________________________________                                    

COMPARATIVE EXAMPLE 1

Each compound was tasted in the same manner as in Example 3.

The results obtained are shown in Table 6 below. In the table, vanillin-PGA represents propylene glycol acetal of vanillin and vanillin-DEA represents diethyl acetal of vanillin.

                  TABLE 6                                                          ______________________________________                                         Compound  Concentration                                                                              Characteristics                                          ______________________________________                                         Vanillin-MPD                                                                             neat        hot, bitter, numbing, lasts                                                    over 4 hours                                             Vanillin-PGA                                                                             neat        hot bitter taste, lasts only                                                   2-3 minutes                                              Vanillin-DEA                                                                             neat        hot bitter taste, lasts only                                                   2-3 minutes                                              Vanillin-DEA                                                                             100 ppm     momentary warm, bitter,                                                        sensation is gone in 30                                                        seconds.                                                 ______________________________________                                    

Vanillin-MPD, vanillin-PGA and vanillin-DEA produce hot sensations at slightly different sites in the mouth. Vanillin-MPD is hotter than vanillin-PGA or -DEA.

EXAMPLE 4 Hard Candy

A hard candy was prepared using 0.0001 to 10% by weight (1 to 100 ppm) of vanillin-MPD as follows:

1 cup of light corn syrup

1 cup of water

2 cups of sugar

1/4 teaspoon of flavoring

1/4 teaspoon of food coloring

0.0001 or 0.1% by weight of vanillin-MPD

The corn syrup, water and sugar were combined in a 2-quart saucepan. The mixture was heated to 300° F. (150° C.) and then removed from the heat. The flavoring, food coloring and vanillin-MPD were then added to the mixture, stirred until blended, poured free-form or into molds and cooled to room temperature to produce a hard candy.

The hard candy thus obtained was tasted and evaluated. The results obtained are shown in Table 7 below.

                  TABLE 7                                                          ______________________________________                                                 Time                                                                   Vanillin-MPD                                                                             2-3 min.  10-15 min.                                                                               30 min.                                                                               90 min.                                   ______________________________________                                          1 ppm    slight hot                                                                               slight hot                                                           taste,    taste,                                                               prickly,  prickly,                                                             numbing   numbing                                                    100 ppm   hot taste,                                                                               hot taste,                                                                               hot taste,                                                                            hot taste,                                          prickly,  prickly,  prickly,                                                                              prickly,                                            numbing   numbing,  numbing,                                                                              numbing                                                       warming   warming                                                              sensation sensation                                                            spread    spread                                                               down to   down to                                                              throat    throat                                           ______________________________________                                    

At 100 ppm, vanillin-MPD has a hot taste with a prickly, numbing effect that is mainly on the tongue. It lasts on the tongue for over 90 minutes. This effect spreads throughout the oral cavity. As a result, there is a warming sensation that spreads to the back of the mouth and down the throat. This warming sensation does not last as long as the hot taste, prickly, numbing effects on the tongue.

While the invention has been described in detail and with reference to specific embodiments thereof, it will be apparent to one skilled in the art that various changes and modifications can be made therein without departing from the spirit and scope thereof. 

What is claimed is:
 1. 4-(1-Menthoxymethyl)-2-phenyl-1,3-dioxolane or a derivative thereof represented by formula (I): ##STR7## wherein R¹ represents a hydrogen atom, a hydroxy group or a lower alkoxy group; R² and R³, which may be the same or different, each represents a hydrogen atom, a hydroxy group, a lower alkoxy group, or when taken together, R² and R³ represents a methylene dioxy group.
 2. 4-(1-Menthoxymethyl)-2-phenyl-1,3-dioxolane or a derivative thereof as in claim 1, wherein R² is a methoxy group and R³ is a hydroxy group.
 3. 4-(1-Menthoxymethyl)-2-phenyl-1,3-dioxolane or a derivative thereof as in claim 1, wherein R² is a hydroxy group and R³ is a hydroxy group.
 4. A flavor composition comprising a flavorant effective amount of 4-(1-menthoxymethyl)-2-phenyl-1,3-dioxolane or a derivative thereof represented by formula (I): ##STR8## wherein R¹ represents a hydrogen atom, a hydroxy group or a lower alkoxy group; R² and R³, which may be the same or different, each represents a hydrogen atom, a hydroxy group, a lower alkoxy group, or, when taken together, R² and R³ represent a methylene dioxy group with an acceptable carrier.
 5. A flavor composition comprising 4-(1-menthoxymethyl)-2-phenyl-1,3-dioxolane or a derivative thereof represented by formula (I) as in claim 4, wherein R² is a methoxy group and R³ is a hydroxy group.
 6. A flavor composition comprising 4-(1-menthoxymethyl)-2-phenyl-1,3-dioxolane or a derivative thereof represented by formula (I) as in claim 4, wherein R² is a hydroxy group and R³ is a hydroxy group.
 7. A flavor composition comprising 4-(1-menthoxymethyl)-2-phenyl-1,3-dioxolane or a derivative thereof represented by formula (I) as in claim 4, wherein said 4-(1-menthoxymethyl)-2-phenyl-1,3-dioxolane or a derivative thereof represented by formula (I) is present in an amount of from 0.0001 to 10% by weight based on the total weight of the composition. 